Ultrasound stimulation of the vagal nerve improves acute septic encephalopathy in mice

Septic encephalopathy (SE) is characterized by symptoms such as coma, delirium, and cognitive dysfunction, and effective therapeutic interventions for SE remain elusive. In this study, we aimed to investigate the potential alleviating effects of vagal nerve stimulation (VNS) on SE-associated signs....

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Main Authors: Yukio Imamura, Hisatake Matsumoto, Jun Imamura, Naoya Matsumoto, Kazuma Yamakawa, Nao Yoshikawa, Yuki Murakami, Satoko Mitani, Junichiro Nakagawa, Tomoki Yamada, Hiroshi Ogura, Jun Oda, Takeshi Shimazu
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-07-01
Series:Frontiers in Neuroscience
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Online Access:https://www.frontiersin.org/articles/10.3389/fnins.2023.1211608/full
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author Yukio Imamura
Yukio Imamura
Yukio Imamura
Yukio Imamura
Hisatake Matsumoto
Jun Imamura
Naoya Matsumoto
Kazuma Yamakawa
Kazuma Yamakawa
Nao Yoshikawa
Yuki Murakami
Yuki Murakami
Satoko Mitani
Satoko Mitani
Junichiro Nakagawa
Tomoki Yamada
Hiroshi Ogura
Jun Oda
Takeshi Shimazu
author_facet Yukio Imamura
Yukio Imamura
Yukio Imamura
Yukio Imamura
Hisatake Matsumoto
Jun Imamura
Naoya Matsumoto
Kazuma Yamakawa
Kazuma Yamakawa
Nao Yoshikawa
Yuki Murakami
Yuki Murakami
Satoko Mitani
Satoko Mitani
Junichiro Nakagawa
Tomoki Yamada
Hiroshi Ogura
Jun Oda
Takeshi Shimazu
author_sort Yukio Imamura
collection DOAJ
description Septic encephalopathy (SE) is characterized by symptoms such as coma, delirium, and cognitive dysfunction, and effective therapeutic interventions for SE remain elusive. In this study, we aimed to investigate the potential alleviating effects of vagal nerve stimulation (VNS) on SE-associated signs. To evaluate our hypothesis, we utilized a mouse model of SE induced by intraperitoneal injection of lipopolysaccharide (0.3 mg per mouse) and administered noninvasive, high-frequency ultrasound VNS. To assess the efficacy of ultrasound VNS, we measured inflammation-related molecules, including the α7 nicotinic acetylcholine receptor (α7nAChR) expression in peritoneal macrophages and plasma interleukin 1β (IL-1β) levels. Consistent with our hypothesis, SE mice exhibited reduced α7nAChR expression in macrophages and elevated IL-1β levels in the blood. Remarkably, VNS in SE mice restored α7nAChR expression and IL-1β levels to those observed in control mice. Furthermore, we evaluated the effects of VNS on survival rate, body temperature, and locomotor activity. SE mice subjected to VNS demonstrated a modest, yet significant, improvement in survival rate, recovery from hypothermia, and increased locomotor activity. To investigate the impact on the brain, we examined the hippocampus of SE mice. In control mice, VNS increased the expression of c-fos, a marker of neuronal electrical excitability, in the hippocampus. In SE mice, VNS led to the restoration of aberrant firing patterns in hippocampal neurons. Additionally, proteomic analysis of hippocampal tissue in SE mice revealed abnormal increases in two proteins, tissue factor (TF) and acyl-CoA dehydrogenase family member 9 (ACAD9), which returned to control levels following VNS. Collectively, our findings support the value of exploring the beneficial effects of ultrasound VNS on SE.
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spelling doaj.art-83e0fcea82834f48b644ea51bef2082f2023-07-17T13:47:24ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2023-07-011710.3389/fnins.2023.12116081211608Ultrasound stimulation of the vagal nerve improves acute septic encephalopathy in miceYukio Imamura0Yukio Imamura1Yukio Imamura2Yukio Imamura3Hisatake Matsumoto4Jun Imamura5Naoya Matsumoto6Kazuma Yamakawa7Kazuma Yamakawa8Nao Yoshikawa9Yuki Murakami10Yuki Murakami11Satoko Mitani12Satoko Mitani13Junichiro Nakagawa14Tomoki Yamada15Hiroshi Ogura16Jun Oda17Takeshi Shimazu18Department of Traumatology and Acute Critical Medicine, Graduate School of Medicine, Osaka University, Osaka, JapanOrganization for Research Initiatives and Development, Doshisha University, Kyoto, JapanDepartment of Architectural and Environmental Planning, Graduate School of Engineering, Kyoto University, Kyoto, JapanDepartment of Hygiene and Public Health, Kansai Medical University, Osaka, JapanDepartment of Traumatology and Acute Critical Medicine, Graduate School of Medicine, Osaka University, Osaka, JapanMolex Corporation, Ltd., Yamato, Kanagawa, JapanDepartment of Traumatology and Acute Critical Medicine, Graduate School of Medicine, Osaka University, Osaka, JapanDepartment of Traumatology and Acute Critical Medicine, Graduate School of Medicine, Osaka University, Osaka, JapanDepartment of Emergency Medicine, Osaka Medical and Pharmaceutical University, Osaka, JapanHuman Health Science, Graduate School of Medicine, Kyoto University, Kyoto, JapanDepartment of Hygiene and Public Health, Kansai Medical University, Osaka, JapanHuman Health Science, Graduate School of Medicine, Kyoto University, Kyoto, JapanHuman Health Science, Graduate School of Medicine, Kyoto University, Kyoto, JapanFaculty of Acupuncture and Moxibustion, Meiji University of Integrative Medicine, Kyoto, JapanDepartment of Traumatology and Acute Critical Medicine, Graduate School of Medicine, Osaka University, Osaka, JapanDepartment of Traumatology and Acute Critical Medicine, Graduate School of Medicine, Osaka University, Osaka, JapanDepartment of Traumatology and Acute Critical Medicine, Graduate School of Medicine, Osaka University, Osaka, JapanDepartment of Traumatology and Acute Critical Medicine, Graduate School of Medicine, Osaka University, Osaka, JapanDepartment of Traumatology and Acute Critical Medicine, Graduate School of Medicine, Osaka University, Osaka, JapanSeptic encephalopathy (SE) is characterized by symptoms such as coma, delirium, and cognitive dysfunction, and effective therapeutic interventions for SE remain elusive. In this study, we aimed to investigate the potential alleviating effects of vagal nerve stimulation (VNS) on SE-associated signs. To evaluate our hypothesis, we utilized a mouse model of SE induced by intraperitoneal injection of lipopolysaccharide (0.3 mg per mouse) and administered noninvasive, high-frequency ultrasound VNS. To assess the efficacy of ultrasound VNS, we measured inflammation-related molecules, including the α7 nicotinic acetylcholine receptor (α7nAChR) expression in peritoneal macrophages and plasma interleukin 1β (IL-1β) levels. Consistent with our hypothesis, SE mice exhibited reduced α7nAChR expression in macrophages and elevated IL-1β levels in the blood. Remarkably, VNS in SE mice restored α7nAChR expression and IL-1β levels to those observed in control mice. Furthermore, we evaluated the effects of VNS on survival rate, body temperature, and locomotor activity. SE mice subjected to VNS demonstrated a modest, yet significant, improvement in survival rate, recovery from hypothermia, and increased locomotor activity. To investigate the impact on the brain, we examined the hippocampus of SE mice. In control mice, VNS increased the expression of c-fos, a marker of neuronal electrical excitability, in the hippocampus. In SE mice, VNS led to the restoration of aberrant firing patterns in hippocampal neurons. Additionally, proteomic analysis of hippocampal tissue in SE mice revealed abnormal increases in two proteins, tissue factor (TF) and acyl-CoA dehydrogenase family member 9 (ACAD9), which returned to control levels following VNS. Collectively, our findings support the value of exploring the beneficial effects of ultrasound VNS on SE.https://www.frontiersin.org/articles/10.3389/fnins.2023.1211608/fullseptic encephalopathyvagal nerveultrasoundα7 nicotinic acetyl choline receptorproteomics
spellingShingle Yukio Imamura
Yukio Imamura
Yukio Imamura
Yukio Imamura
Hisatake Matsumoto
Jun Imamura
Naoya Matsumoto
Kazuma Yamakawa
Kazuma Yamakawa
Nao Yoshikawa
Yuki Murakami
Yuki Murakami
Satoko Mitani
Satoko Mitani
Junichiro Nakagawa
Tomoki Yamada
Hiroshi Ogura
Jun Oda
Takeshi Shimazu
Ultrasound stimulation of the vagal nerve improves acute septic encephalopathy in mice
Frontiers in Neuroscience
septic encephalopathy
vagal nerve
ultrasound
α7 nicotinic acetyl choline receptor
proteomics
title Ultrasound stimulation of the vagal nerve improves acute septic encephalopathy in mice
title_full Ultrasound stimulation of the vagal nerve improves acute septic encephalopathy in mice
title_fullStr Ultrasound stimulation of the vagal nerve improves acute septic encephalopathy in mice
title_full_unstemmed Ultrasound stimulation of the vagal nerve improves acute septic encephalopathy in mice
title_short Ultrasound stimulation of the vagal nerve improves acute septic encephalopathy in mice
title_sort ultrasound stimulation of the vagal nerve improves acute septic encephalopathy in mice
topic septic encephalopathy
vagal nerve
ultrasound
α7 nicotinic acetyl choline receptor
proteomics
url https://www.frontiersin.org/articles/10.3389/fnins.2023.1211608/full
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